Chemically modified peptides based on the membrane proximal external region of HIV-1 envelope induce high titer, epitope specific non-neutralizing antibodies in rabbits. Broadly neutralizing monoclonal antibodies (bNAbs), 2F5 and 4E10, bind to the membrane proximal external region (MPER) of gp41 and also cross react with phospholipids. In this study, we investigated if chemical modifications on MPER adjacent to 2F5 and 4E10 epitopes would break tolerance using mimetics of inflammation-associated post-translational modifications to induce 2F5- and 4E10-like bNAbs. We synthesized a series of chemically modified peptides spanning the MPER. Serine, threonine and tyrosine residues in the peptides were modified with sulfate, phosphate or nitrate moieties and presented in liposomes for rabbit immunizations.
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